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Inhibition of early platelet-derived growth factor responses in BALB/c-3T3 cells by interferon
M Zagari1, J R Hepler, C Harris
1Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599.
Abstract:
Stimulation of total inositol phosphate production, alteration of cytosolic free calcium [( Ca++]i), vinculin disruption from adhesion plaques, and DNA synthesis caused by PDGF were examined in normal and INF pretreated density arrested BALB/c-3T3 fibroblasts. In normal cells, PDGF caused an increase in total inositol phosphates, a rapid, transient increase in [Ca++]i, disappearance of vinculin from adhesion plaques, and stimulation of DNA synthesis. Pretreatment of cells with INF inhibited PDGF-stimulated increases in [Ca++]i, vinculin disruption from adhesion plaques, and DNA synthesis, but had no effect on PDGF-induced increase in total inositol phosphate levels. These findings suggest that INF prevents entry of quiescent BALB/c-3T3 cells into G1 by inhibiting PDGF-induced release of Ca++ from intracellular stores.
Insights
Interferon (IFN) pretreatment inhibits platelet-derived growth factor (PDGF)-stimulated calcium release and DNA synthesis in BALB/c-3T3 fibroblasts. This suggests IFN prevents cell cycle entry by blocking intracellular calcium release.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Platelet-derived growth factor (PDGF) is a potent mitogen that stimulates cellular processes.
- Interferon (IFN) is known to modulate cellular responses to growth factors.
- Understanding the interplay between PDGF and IFN is crucial for cell cycle regulation research.
Purpose of the Study:
- To investigate the effects of IFN pretreatment on PDGF-stimulated cellular responses in BALB/c-3T3 fibroblasts.
- To elucidate the role of intracellular calcium and inositol phosphate production in PDGF signaling.
- To determine if IFN inhibits PDGF-induced cell cycle progression.
Main Methods:
- BALB/c-3T3 fibroblasts were arrested at the G0/G1 phase.
- Cells were pretreated with IFN before stimulation with PDGF.
- Measurements included total inositol phosphate production, cytosolic free calcium levels ([Ca++]i), vinculin localization, and DNA synthesis.
Main Results:
- PDGF stimulation in normal cells increased inositol phosphates, [Ca++]i, disrupted vinculin, and stimulated DNA synthesis.
- IFN pretreatment inhibited PDGF-induced increases in [Ca++]i, vinculin disruption, and DNA synthesis.
- IFN pretreatment did not affect PDGF-induced total inositol phosphate production.
Conclusions:
- IFN inhibits PDGF-induced entry of quiescent BALB/c-3T3 cells into the G1 phase.
- The inhibitory mechanism involves blocking the PDGF-stimulated release of calcium from intracellular stores.
- IFN's effect is downstream of inositol phosphate production but upstream of calcium release.